Formation and In Vitro Evaluation of a Deep Eutectic Solvent Conversion Film on Biodegradable Magnesium Alloy.
The chemical conversion films from deep eutectic solvents (DESs) have recently been shown to reduce the corrosion rate of magnesium alloys, which are recognized as a kind of promising materials applied in the human body. However, the biocompatibility of the conversion films has not been investigated. This study proposes an uncommon DES system composed of lithium chloride and urea to fabricate the chemical conversion films on Mg and its alloy. The fabrication process of the conversion film is facile, which is performed by the heat treatment of the substrate in the DES at about 200 °C for 30 min. It is found that the thermal decomposition of the DES can release hydrogen, which diffuses into the Mg substrate to form MgH2-based conversion films. The DES conversion film possesses a porous structure on pure Mg, whereas it becomes dense on the alloy with some cracks. X-ray photoelectron spectroscopy shows that MgCO3 and oxides also exist in the DES conversion films, which depends on the substrate. Electrochemical corrosion test and in vitro biocompatibility tests, including hemolysis, cytotoxicity, antibacterial, and cytoskeleton staining experiments, are performed in a simulated body environment, which shows that the corrosion resistance and biocompatibility of the substrates have been improved significantly. We expect that the DES heat treatment method will be applied to the fabrication of corrosion-resistant and biocompatible surfaces for biodegradable Mg alloys.


Therapeutic effects of menstrual blood-derived endometrial stem cells on mouse models of streptozotocin-induced type 1 diabetes.
Type 1 diabetes (T1D), a chronic metabolic and autoimmune disease, seriously endangers human health. In recent years, mesenchymal stem cell (MSC) transplantation has become an effective treatment for diabetes. Menstrual blood-derived endometrial stem cells (MenSC), a novel MSC type derived from the decidual endometrium during menstruation, are expected to become promising seeding cells for diabetes treatment because of their noninvasive collection procedure, high proliferation rate and high immunomodulation capacity. To comprehensively compare the effects of MenSC and umbilical cord-derived MSC (UcMSC) transplantation on T1D treatment, to further explore the potential mechanism of MSC-based therapies in T1D, and to provide support for the clinical application of MSC in diabetes treatment. A conventional streptozotocin-induced T1D mouse model was established, and the effects of MenSC and UcMSC transplantation on their blood glucose and serum insulin levels were detected. The morphological and functional changes in the pancreas, liver, kidney, and spleen were analyzed by routine histological and immunohistochemical examinations. Changes in the serum cytokine levels in the model mice were assessed by protein arrays. The expression of target proteins related to pancreatic regeneration and apoptosis was examined by western blot. MenSC and UcMSC transplantation significantly improved the blood glucose and serum insulin levels in T1D model mice. Immunofluorescence analysis revealed that the numbers of insulin+ and CD31+ cells in the pancreas were significantly increased in MSC-treated mice compared with control mice. Subsequent western blot analysis also showed that vascular endothelial growth factor (VEGF), Bcl2, Bcl-xL and Proliferating cell nuclear antigen in pancreatic tissue was significantly upregulated in MSC-treated mice compared with control mice. Additionally, protein arrays indicated that MenSC and UcMSC transplantation significantly downregulated the serum levels of interferon γ and tumor necrosis factor α and upregulated the serum levels of interleukin-6 and VEGF in the model mice. Additionally, histological and immunohistochemical analyses revealed that MSC transplantation systematically improved the morphologies and functions of the liver, kidney, and spleen in T1D model mice. MenSC transplantation significantly improves the symptoms in T1D model mice and exerts protective effects on their main organs. Moreover, MSC-mediated angiogenesis, antiapoptotic effects and immunomodulation likely contribute to the above improvements. Thus, MenSC are expected to become promising seeding cells for clinical diabetes treatment due to their advantages mentioned above.


An optimized algorithm for flux estimation from isotopomer distribution in glucose metabolites.
Analysis of the conversion of (13)C glucose within the metabolic network allows the evaluation of the biochemical fluxes in interconnecting metabolic pathways. Such analyses require solving hundreds of equations with respect to individual isotopomer concentrations, and this assumes applying special software even for constructing the equations. The algorithm, proposed by others could be improved. A C-code linked to the program written in Mathematica (Wolfram Research Inc.), constructs and solves differential equations for all isotopomer concentrations, using the general enzyme characteristics (K(m), equilibrium constant, etc.). This code uses innovative algorithm of determination for the isotopomers-products, thus essentially decreasing the computation time. Feasible metabolic fluxes are provided by the parameters of enzyme kinetics found from the data fitting. The software effectively evaluates metabolic fluxes based on the measured isotopomer distribution, as was illustrated by the analysis of glycolysis and pentose phosphate cycle. The mechanism of transketolase and transaldolase catalysis was shown to induce a specific kind of isotopomer re-distribution, which, despite the significance of its effect, usually is not taken into account. The software could be freely downloaded from the site: http://bq.ub.es/bioqint/label_distribution/.


A corrugated epsilon-nearzero saturable absorber for a high-performance 1.3 μm solid-state bulk laser.
Epsilon-near-zero (ENZ) materials with vanishing permittivity exhibit unprecedented optical nonlinearity within subwavelength propagation lengths in the ENZ region, making them promising photoelectric materials that have achieved exciting results in ultrafast pulse laser modulations. In this study, we fabricated a novel saturable absorber (SA) based on a corrugated indium tin oxide (CITO) film with a symmetrical geometry using a low-cost self-assembly process. The strong saturable absorption of the CITO film triggered by the ENZ effect at normal incidence was comparable to that of the planar indium tin oxide (ITO) film at an optimal 60° incidence (TM polarization) at 1340 nm. In addition, the strong nonlinear optical properties of the CITO film were not limited by the incident angle and polarization state of the pump laser over a wide range of 0-20°. Benefiting from the excellent saturable absorption of CITO-based SA at normal incidence, a Q-switching operation with CITO-based SA at 1.34 μm was achieved in a Nd:YVO4 solid-state laser system, obtaining pulses of a duration of 85.6 ns, which was one order of magnitude narrower than that of the planar ITO-based SA. This study presents a new strategy for developing high-performance ENZ-based SAs and ultrafast lasers.


[Outline biography of a forgotten Polish doctor from Estonia].
The paper presents the figure of Polish doctor Władysław Wawrzyniec Mierzejewski who was born in 1841 in the province of Witebsk. He studied medicine in Petersburg. After graduation in the field of gynecology followed by the achievement of MD, he moved to the city of Kuressaare on the Saaremaa Island in 1876. That year he established a natural therapy clinic there and treated female patients from Petersburg, Tallin and Dorpat. The clinic was taken over by his son Gonzaga George Mierzejewski, a gynecologist himself. The clinic was destroyed during II World War in 1941. At present, the former location of the balneology clinic is commemorated with a stone with a plate for the memory of Polish doctors.


Recent molecular approaches to understanding astrocyte function in vivo.
Astrocytes are a predominant glial cell type in the nervous systems, and are becoming recognized as important mediators of normal brain function as well as neurodevelopmental, neurological, and neurodegenerative brain diseases. Although numerous potential mechanisms have been proposed to explain the role of astrocytes in the normal and diseased brain, research into the physiological relevance of these mechanisms in vivo is just beginning. In this review, we will summarize recent developments in innovative and powerful molecular approaches, including knockout mouse models, transgenic mouse models, and astrocyte-targeted gene transfer/expression, which have led to advances in understanding astrocyte biology in vivo that were heretofore inaccessible to experimentation. We will examine the recently improved understanding of the roles of astrocytes - with an emphasis on astrocyte signaling - in the context of both the healthy and diseased brain, discuss areas where the role of astrocytes remains debated, and suggest new research directions.


Electrical current nanogeneration driven by spontaneous nanofluidic oscillations.
Exploiting natural phenomena is a central route for providing electricity to sustainably drive wearable electronics. Here we report a nano-scale water-driven energy generator that produces tiny electrical currents from spontaneous wetting-drying oscillations in mesoporous thin films. The system was fabricated with a wormlike mesoporous silica film, which was packed in between Cu and silicon contacts. The nanogenerator runs autonomously when a water droplet is laid over the film close to the Cu electrode, as water infiltration into the film under the electrode produces a direct-current. Wetting-drying cycles, which are spontaneously triggered by water evaporation, are perfectly correlated to the generated electrical current. The autonomous water displacement through the film yields a sustained energy conversion until the droplet reservoir vanishes. This novel water-driven nanogenerator opens new alternatives for versatile, mobile and cost-effective self-powering of nanosystems and nanodevices.


Novel phase change behavior of n-eicosane in nanoporous silica: emulsion template preparation and structure characterization using small angle X-ray scattering.
Silica microcapsules with hierarchical pore structure are prepared using a one step emulsion templated hydrolysis method. Silica particles of around 100 nm with percolated nanosized pores are self-assembled into micrometer scale spherical shells. The porous structure serves as an ideal host for shape stabilization of melted organic compounds. Small angle X-ray scattering (SAXS) results show that the n-eicosane encapsulated in nanoporous silica consists of mass fractal structure with a fractal dimension of 2.1. n-Eicosane encapsulated in the nanosized pores exhibits novel phase change behavior. A large melting point drop from 37.0 to 28.8 °C is observed, which is attributed to the strong interaction between the n-eicosane molecules and the silica skeleton.


Rep helicase suppresses short-homology-dependent illegitimate recombination in Escherichia coli.
To study roles of Rep helicase in short-homology-dependent illegitimate recombination, we examined the effect of a rep mutation on illegitimate recombination and found that the frequency of spontaneous illegitimate recombination is enhanced by the rep mutation. In addition, illegitimate recombination was synergistically enhanced by the rep mutation and UV irradiation, showing that Rep helicase plays a role in suppression of spontaneous as well as UV-induced illegitimate recombination. The defect in RecQ helicase also has a synergistic effect on the increased illegitimate recombination in the rep mutant. It was also found that the illegitimate recombination induced by the rep mutation is independent of the RecA function with or without UV irradiation. Nucleotide sequence analyses of the recombination junctions showed that the illegitimate recombination induced by the rep mutation mostly takes place between short homologous sequences. Based on the fact that the defect of Rep helicase induces replication arrest during replication, resulting in the formation of DNA double-strand breaks, we propose a model for illegitimate recombination, in which double-strand breaks caused by defect of Rep helicase promotes illegitimate recombination via short-homology-dependent-end-joining. In addition, the mechanism of synergistic action between the rep mutation and UV irradiation on illegitimate recombination is discussed.


Hepatic arterial buffer response in monochorionic diamniotic pregnancies with twin-to-twin transfusion syndrome.
Hepatic arterial buffer response (HABR) is an important regulatory process for hepatic blood flow. Its activity has been described in some fetal adverse conditions but in twin-to-twin transfusion syndrome (TTTS) it is unknown if such response is present. The aim of this study is to test the hypothesis that HABR operates in monochorionic diamniotic twins (MCDA) with TTTS. Hepatic artery pulsatility index (PI) and peak systolic velocity (PSV) were measured prospectively in 64 MCDA pregnancies. 43 without TTTS (group 1) and in 21 pregnancies with TTTS (group 2). We calculated ratios for PI (HAPI-ratio) and PSV (HAV-ratio) between recipient and donor in group 2 or bigger and smaller fetus in group 1 and compared groups. The association of HAV-ratio and HAPI ratio with TTTS, relation with other fetal Dopplers and reliability of measurement by a single operator were investigated. HAV-ratio and HAPI-ratio appears to be independent from fetal Dopplers, estimated weight and gestational age. In group 2, HAV-ratio is lower than group 1 (p<0.001, 95% CI 0.443-0.643). In group 1 the mean HAV-ratio is 1.014 (±0.021) while in group 2 is 0.47 (±0.035). HAPI-ratio is lower in group 2 than in group 1 although this difference was not significant (p=0.066, 95% CI -0.007-0.231). A good reliability of measurements of hepatic artery PSV and PI was demonstrated by intraclass correlation coefficient analysis (ICC 0.971 95% CI 0.963-0.977, p<0.001 and ICC 0.694 95% CI 0.596-0.772, p<0.001, respectively). Monochorionic pregnancies with TTTS are associated with lower HAV-ratios. This could be explained by an active HABR.


Stable and Efficient Dye-Sensitized Solar Cells and Supercapacitors Developed Using Ionic-Liquid-Doped Biopolymer Electrolytes.
An ionic liquid (IL) 1-ethyl, 2-methyl imidazolium thiocyanate incorporated biopolymer system is reported in this communication for applications in dual energy devices, i.e., electric double-layer capacitors (EDLCs) and dye-sensitized solar cells (DSSCs). The solution caste method has been used to synthesize ionic-liquid-incorporated biopolymer electrolyte films. The IL mixed biopolymer electrolytes achieve high ionic conductivity up to the order of 10-3 S/cm with good thermal stability above 250 °C. Electrical, structural, and optical studies of these IL-doped biopolymer electrolyte films are presented in detail. The performance of EDLCs was evaluated using low-frequency electrochemical impedance spectroscopy, cyclic voltammetry, and constant current charge-discharge, while that of DSSCs was assessed using J-V characteristics. The EDLC cells exhibited a high specific capacitance of 200 F/gram, while DSSCs delivered 1.53% efficiency under sun conditions.


Using computational phantoms to improve delivery of Tumor Treating Fields (TTFields) to patients.
This paper reviews the state-of-the-art in simulation-based studies of Tumor Treating Fields (TTFields) and highlights major aspects of TTFields in which simulation-based studies could affect clinical outcomes. A major challenge is how to simulate multiple scenarios rapidly for TTFields delivery. Overcoming this challenge will enable a better understanding of how TTFields distribution is correlated with disease progression, leading to better transducer array designs and field optimization procedures, ultimately improving patient outcomes.


Synthesis of bisected glycoforms of recombinant IFN-beta by overexpression of beta-1,4-N-acetylglucosaminyltransferase III in Chinese hamster ovary cells.
Genetic engineering of oligosaccharide biosynthesis pathways in mammalian cells makes possible generation of new recombinant glycoproteins of potential importance in the biopharmaceutical industry. Most prior investigations of glycosylation engineering of secreted heterologous glycoproteins involve terminal steps of oligosaccharide biosynthesis. In particular, increasing the frequency of bisected structures within the glycoform distribution has not before been considered. A Chinese hamster ovary (CHO) cell line capable of producing bisected oligosaccharides on glycoproteins was created by overexpression of a recombinant N-acetylglucosaminyltransferase III (GnT-III). Interferon beta (IFN-beta) was chosen as a model and potential therapeutic secreted heterologous protein to demonstrate the effect of recombinant GnT-III-expression on product glycosylation. IFN-beta with bisected oligosaccharides was produced by the GnT-III-engineered CHO cells but not by the unmodified parental cell line.


Pregnancy rates in varying age groups after in vitro fertilization: a comparison of follitropin alfa (Gonal F) and follitropin beta (Follistim).
Our purpose was to assess the efficacy of two recombinant follicle-stimulating hormones, follitropin beta (Follistim, Organon, West Orange, NJ) and follitropin alfa (Gonal F, Serono, Norwell, Mass) on pregnancy rates in varying age groups of women undergoing in vitro fertilization (IVF). Three hundred sixty-five IVF cycles were retrospectively compared, 233 by use of follitropin beta and 132 by use of follitropin alfa, both after gonadotropin-releasing hormone agonist down-regulation. Assignment to each medication was indiscriminate. The primary outcome measured was pregnancy evidenced by fetal heartbeat on ultrasonography. Secondary outcomes included days of stimulation, ampules per patient cycle, estradiol level on the day of human chorionic gonadotropin administration, total follicles present on the day of human chorionic gonadotropin administration, follicles greater than 14 mm, oocytes retrieved, mature eggs, fertilization rate, and embryos transferred. Outcomes were stratified by age, including women less than 36 years old, 36 to 39 years old, and more than 39 years old. There was no significant difference between follitropin beta and follitropin alfa in either the primary or secondary outcomes, although the pregnancy rate was significantly decreased with advancing age. Success rates are similar, when stratified by age, in women undergoing IVF with either follitropin beta or follitropin alfa.


[Biomechanical evaluation of titanium mesh with anterior plate fixation or ilium autograft in anterior cervical decompression].
To evaluate the biomechanical characteristics of titanium mesh with anterior plate fixation or ilium autograft in anterior cervical decompression. Six fresh cervical spine specimens (C3-7) of young cadaver were used in the biomechanical test. After C5, C5,6 and C4-6 were given vertebrectomy, ilium autograft and titanium mesh with anterior plate fixation were performed. Their stabilities of flexion, bilateral axial rotation, the lateral bending and the extension were tested. Intact cervical spine specimens served as control group. Ilium autograft improved the stability of the unstable cervical vertebrae and decreased the flexion, the lateral bending or the extension, showing a significant difference when compared with control group (P<0.05). Whereas, axial rotational motion was decreased insignificantly (P>0.05). Titanium mesh with anterior plate fixation improved the stability of the unstable spine and decreased the flexion,the bilateral axial rotation,the lateral bending or the extension, showing a significant difference when compared with control group (P<0.05). The vertebrectomy and anterior cervical fusion by ilium autograft was the least stable construct of all modes tested,and the titanium mesh implantation is stable than the intact cervical sample.


Modeling the vacuolar storage of malate shed lights on pre- and post-harvest fruit acidity.
Malate is one of the most important organic acids in many fruits and its concentration plays a critical role in organoleptic properties. Several studies suggest that malate accumulation in fruit cells is controlled at the level of vacuolar storage. However, the regulation of vacuolar malate storage throughout fruit development, and the origins of the phenotypic variability of the malate concentration within fruit species remain to be clarified. In the present study, we adapted the mechanistic model of vacuolar storage proposed by Lobit et al. in order to study the accumulation of malate in pre and postharvest fruits. The main adaptation concerned the variation of the free energy of ATP hydrolysis during fruit development. Banana fruit was taken as a reference because it has the particularity of having separate growth and post-harvest ripening stages, during which malate concentration undergoes substantial changes. Moreover, the concentration of malate in banana pulp varies greatly among cultivars which make possible to use the model as a tool to analyze the genotypic variability. The model was calibrated and validated using data sets from three cultivars with contrasting malate accumulation, grown under different fruit loads and potassium supplies, and harvested at different stages. The model predicted the pre and post-harvest dynamics of malate concentration with fairly good accuracy for the three cultivars (mean RRMSE = 0.25-0.42). The sensitivity of the model to parameters and input variables was analyzed. According to the model, vacuolar composition, in particular potassium and organic acid concentrations, had an important effect on malate accumulation. The model suggested that rising temperatures depressed malate accumulation. The model also helped distinguish differences in malate concentration among the three cultivars and between the pre and post-harvest stages by highlighting the probable importance of proton pump activity and particularly of the free energy of ATP hydrolysis and vacuolar pH. This model appears to be an interesting tool to study malate accumulation in pre and postharvest fruits and to get insights into the ecophysiological determinants of fruit acidity, and thus may be useful for fruit quality improvement.


A Methionine Residue Promotes Hyperoxidation of the Catalytic Cysteine of Mouse Methionine Sulfoxide Reductase A.
Methionine sulfoxide reductase A (msrA) reduces methionine sulfoxide in proteins back to methionine. Its catalytic cysteine (Cys72-SH) has a low pKa that facilitates oxidation by methionine sulfoxide to cysteine sulfenic acid. If the catalytic cycle proceeds efficiently, the sulfenic acid is reduced back to cysteine at the expense of thioredoxin. However, the sulfenic acid is vulnerable to "irreversible" oxidation to cysteine sulfinic acid that inactivates msrA (hyperoxidation). We observed that human msrA is resistant to hyperoxidation while mouse msrA is readily hyperoxidized by micromolar concentrations of hydrogen peroxide. We investigated the basis of this difference in susceptibility to hyperoxidation and established that it is controlled by the presence or absence of a Met residue in the carboxyl-terminal domain of the enzyme, Met229. This residue is Val in human msrA, and when it was mutated to Met, human msrA became sensitive to hyperoxidation. Conversely, mouse msrA was rendered insensitive to hyperoxidation when Met229 was mutated to Val or one of five other residues. Positioning of the methionine at residue 229 is not critical, as hyperoxidation occurred as long as the methionine was located within the group of 14 carboxyl-terminal residues. The carboxyl domain of msrA is known to be flexible and to have access to the active site, and Met residues are known to form stable, noncovalent bonds with aromatic residues through interaction of the sulfur atom with the aromatic ring. We propose that Met229 forms such a bond with Trp74 at the active site, preventing formation of a protective sulfenylamide with Cys72 sulfenic acid. As a consequence, the sulfenic acid is available for facile, irreversible oxidation to cysteine sulfinic acid.


End-Triassic mass extinction started by intrusive CAMP activity.
The end-Triassic extinction is one of the Phanerozoic's largest mass extinctions. This extinction is typically attributed to climate change associated with degassing of basalt flows from the central Atlantic magmatic province (CAMP). However, recent work suggests that the earliest known CAMP basalts occur above the extinction horizon and that climatic and biotic changes began before the earliest known CAMP eruptions. Here we present new high-precision U-Pb ages from CAMP mafic intrusive units, showing that magmatic activity was occurring ∼100 Kyr ago before the earliest known eruptions. We correlate the early magmatic activity with the onset of changes to the climatic and biotic records. We also report ages from sills in an organic rich sedimentary basin in Brazil that intrude synchronously with the extinction suggesting that degassing of these organics contributed to the climate change which drove the extinction. Our results indicate that the intrusive record from large igneous provinces may be more important for linking to mass extinctions than the eruptive record.


Metacognitive Awareness of Facial Affect in Higher-Functioning Children and Adolescents with Autism Spectrum Disorder.
Higher-functioning participants with and without autism spectrum disorder (ASD) viewed a series of face stimuli, made decisions regarding the affect of each face, and indicated their confidence in each decision. Confidence significantly predicted accuracy across all participants, but this relation was stronger for participants with typical development than participants with ASD. In the hierarchical linear modeling analysis, there were no differences in face processing accuracy between participants with and without ASD, but participants with ASD were more confident in their decisions. These results suggest that individuals with ASD have metacognitive impairments and are overconfident in face processing. Additionally, greater metacognitive awareness was predictive of better face processing accuracy, suggesting that metacognition may be a pivotal skill to teach in interventions.


Membrane channel interactions underlying rat subthalamic projection neuron rhythmic and bursting activity.
A computational model of the rat subthalamic nucleus projection neuron is constructed using electrophysiological and morphological data and a restricted set of channel specifications. The model cell exhibits a wide range of electrophysiological behaviors characteristic of rat subthalamic neurons. It reveals that a key set of three channels play a primary role in distinguishing behaviors: a high-voltage-activated calcium channel (Cav 1.2.-1.3), a low-voltage-activated calcium channel (Cav 3.-), and a small current calcium-activated potassium channel (KCa 2.1-2.3). Short and long posthyperpolarization rebound responses, low-frequency rhythmic bursting (< 1 Hz), higher-frequency rhythmic bursting (4-7 Hz), and slow action and depolarizing potentials are behaviors all mediated by the interaction of these channels. This interaction can generate a robust calcium-dependent extended depolarization in the dendrites (a depolarizing plateau). The diversity observed in the rat subthalamic physiology (such as short or long rebounds, or the presence of low-frequency rhythmic busting) can arise from alterations in both the density and distributions of these channel types and, consequently, their ability to generate this depolarizing plateau. A number of important predictions arise from the model. For example, blocking or disrupting the low-voltage-activated Cav 3.- calcium current should mute the emergence of rebound responses and rhythmic bursting. Conversely, increasing this channel current via large hyperpolarizing potentials in combination with partial blockade of the high-voltage-activated calcium channels should lead to the more experimentally elusive in vitro high-frequency bursting.


[DIFFERENTIATION AND PROLIFERATION POTENTIAL OF NEURAL STEM CELLS IN SUBVENTRICULAR ZONE OF MICE IN VITRO].
To establish the system of isolation, cultivation, and identification of the neural stem cells (NSCs) from subventricular zone (SVZ) of neonatal mice so as to seek for the appropriate seed cells for potential therapeutic interventions of neurological disorders. NSCs were isolated enzymatically and mechanically from SVZ of neonatal mice and cultured. The cellular morphology was observed by inverted microscopy. Immunocytochemical stainings of anti-Nestin and anti-SOX-2 were used to identify NSCs of passage 3. To study the differentiation of NSCs, NSCs were plated into 24-wells in the medium supplemented without epidermal growth factor (EGF) and basic fibroblastic growth factor (bFGF) for 3 or 7 days. To compare the differentiation and proliferation potential of NSCs with different cultivation time, the BrdU pulse-labeling method and MTT test were used. To identify neurons and astrocytes, the anti-β-tubulin III (Tuj-1) and anti-glial fibrillary acidic protein (GFAP) staining were used. The cells of the SVZ can be isolated and cultured in vitro, and these cells began to form neurospheres after cultured for 3 days at primary passage. While cultured for 7 days, these cells formed more neurospheres, and the volume of the neurospheres became bigger than neurospheres cultured for 3 days. In addition, after cultured for 7 days, the phenomena of fusion of neurospheres and adherent differentiation of neurospheres were observed under inverted microscope. These cells were provided with the typical phenotype of NSCs. The immunofluorescence staining results revealed that these cells showed positive immunoreactivity to Nestin and SOX-2. During the 4 hours BrdU pulse, the number of proliferated NSCs cultured for 3 days (75.817 ± 2.961) was significantly higher than that of NSCs cultured for 7 days (56.600 ± 4.881) (t = 3.366, P = 0.028). The results of MTT assay revealed that the absorbance (A) value of NSCs cultured for 3 days (0.478 ± 0.025) was significantly higher than that of NSCs which were cultured for 7 days (0.366 ± 0.032)(t = 2.752, P = 0.011). After cultivated without EGF and bFGF, the percentage of Tuj-1 and GFAP positive cells in NSCs was 23.1% ± 3.7% and 23.7% ± 3.8% for 3 days and was 40.1% ± 3.6% and 37.1% ± 4.5% for 7 days, respectively, all showing significant differences (t = 3.285, P = 0.030; t = 3.930, P = 0.017). The NSCs from SVZ of neonatal mice have potentials of self-renewal and multipotential differentiation in vitro. With different cultivation time, the potentials of proliferation and differentiation of NSCs are different.


A Brief History of the Encoding of Hand Position by the Cerebral Cortex: Implications for Motor Control and Cognition.
Encoding hand position by the cerebral cortex is essential not only for the neural representation of the body image but also for different actions based on eye-hand coordination. These include reaching for visual objects as well as complex movement sequences, such as tea-making, tool use, and object construction, among many others. All these functions depend on a continuous refreshing of the hand position representation, relying on both predictive signaling and afferent information. The hand position influence on neural activity in the parietofrontal system, together with eye position signals, are the basic elements of an eye-hand matrix from which all the above functions can emerge and could be regarded as key features of a network with several entry points, command nodes and outflow pathways, as confirmed by the discovery of a direct parietospinal projection for the control of hand action. The integrity of this system is crucial for daily life, as testified by the consequences of cortical lesions, spanning from severe paralysis to complex forms of apraxia. In this review, I will sketch my personal understanding of the scientific and conceptual trajectory of a line of investigation with many unexpected influences on cortical function and disease, from motor behavior to cognition.


Studies on vaccine control and immunogenicity of polysaccharides of Streptococcus pneumoniae.
An immunoelectrophoretic method was devised for quantitation of 14 polysaccharide components in the pneumococcal vaccine, and for determination of their stability in the final container. By this method the individual polysaccharide types, 1, 2, 3, 4, 6A, 8, 9N, 12F, 18C, 19F, 23F, and 25 (Danish nomenclature), were found to be present at 80%-123% of the manufacturer's listed concentrations. Pneumococcal polysaccharide types 3, 6A, 9N, and 19F, used as representative types, were heated at 37C for 24 hr and stored at 4 C. The concentrations of these polysaccharides remained constant over a 12-month period, and the molecular sizes of types 3 and 9N were stable during storage. In contrast, the molecular sizes of types 6A and 19F declined gradually during the 12-month storage period. Pneumococcal type 19F polysaccharide was conjugated to various proteins, i.e., bovine serum albumin, human immunoglobulin, and pneumococcal R61 cell wall protein, by the method of reductive amination. Immunization of mice with 19F polysaccharide-protein conjugates resulted in formation of more antibody than was found in the control group. Young mice exposed to pneumococcal type 19F polysaccharide-protein conjugate during gestation and suckling exhibited a greater antibody response than did mice that received no type 19F polysaccharide-protein conjugate while suckling or received the conjugate only when they were only two weeks of old.


Connecting the Human Microbiome and Pancreatic Cancer.
Pancreatic cancer is a deadly disease that is increasing in incidence throughout the world. There are no clear causal factors associated with the incidence of pancreatic cancer; however, some correlation to smoking, diabetes and alcohol has been described. Recently, a few studies have linked the human microbiome (oral and gastrointestinal tract) to pancreatic cancer development. A perturbed microbiome has been shown to alter normal cells while promoting cancer-related processes such as increased cell signaling, immune system evasion and invasion. In this article, we will review in detail the alterations within the gut and oral microbiome that have been linked to pancreatic cancer and explore the ability of other microbiomes, such as the lung and skin microbiome, to contribute to disease development. Understanding ways to identify a perturbed microbiome can result in advancements in pancreatic cancer research and allow for prevention, earlier detection and alternative treatment strategies for patients.


Accidental intrathecal injection of bupivacaine and dextran.
The case is reported of a patient who received an accidental intrathecal injection of a mixture containing 0.375% plain bupivacaine in dextran following a paravertebral block. From the duration of anaesthesia produced, it is suggested that the addition of dextran to a solution of bupivacaine does not potentiate the action of subarachnoid bupivacaine.


High temporal resolution aberrometry in a 50-eye population and implications for adaptive optics error budget.
We formed a database gathering the wavefront aberrations of 50 healthy eyes measured with an original custom-built Shack-Hartmann aberrometer at a temporal frequency of 236 Hz, with 22 lenslets across a 7-mm diameter pupil, for a duration of 20 s. With this database, we draw statistics on the spatial and temporal behavior of the dynamic aberrations of the eye. Dynamic aberrations were studied on a 5-mm diameter pupil and on a 3.4 s sequence between blinks. We noted that, on average, temporal wavefront variance exhibits a n-2 power-law with radial order n and temporal spectra follow a f-1.5 power-law with temporal frequency f. From these statistics, we then extract guidelines for designing an adaptive optics system. For instance, we show the residual wavefront error evolution as a function of the number of corrected modes and of the adaptive optics loop frame rate. In particular, we infer that adaptive optics performance rapidly increases with the loop frequency up to 50 Hz, with gain being more limited at higher rates.


[Impaired balance of the lung proteolytic system in patients with pneumoconiosis and chronic dust-induced bronchitis].
The activity of neutrophilic elastase and the level of its major inhibitor--an alpha 1-inhibitor of proteinases were studied to evaluate the protease-antiprotease system in the bronchoalveolar lavage fluid (BALF) of patients with chronic dust-induced bronchitis (CDB) and pneumoconiosis (PC). It was found that CDB, as compared with PC, was characterized by a higher elastase activity in the BALF (70%) and that there were a larger number of patients with elastase activity (40%), which correlated with the detection rate of emphysema. Free elastase activity and relative proteinase alpha 1-inhibitor deficiency suggest that the BALF protease-antiprotease system is impaired in patients with CDB and PC, which is more pronounced in patients with CDB.


[Chinese expert consensus on the perioperative management of minimally invasive glaucoma surgery with subconjunctival implants (2023)].
Minimally invasive glaucoma surgery (MIGS) is widely used in China because of its effective reduction of intraocular pressure, small incisions, few surgical complications, and quick postoperative recovery. In order to regulate and promote the clinical application of MIGS, the Glaucoma Group of Ophthalmology Branch of Chinese Medical Association has formed consensus opinions on the clinical application and perioperative management of MIGS with subconjunctival implants on the basis of domestic and foreign research results and clinical practice, providing reference and guidance for clinical work.


Further pharmacological evidence of nuclear factor-kappa B pathway involvement in bradykinin B1 receptor-sensitized responses in human umbilical vein.
Bradykinin (BK) B(1) receptors are thought to exert a pivotal role in maintaining and modulating inflammatory processes. They are not normally present under physiological situations but are induced under physiopathological conditions. In isolated human umbilical vein (HUV), a spontaneous BK B(1) receptor up-regulation and sensitization process has been demonstrated. Based on pyrrolidine-dithiocarbamate inhibition, it has been proposed that this phenomenon is dependent on nuclear factor-kappaB (NF-kappaB) activation. The aim of this study was to further evaluate the NF-kappaB pathway involvement on BK B(1) receptor sensitization in isolated HUV, using several pharmacological tools. In 5-h incubated rings, either the I-kappaB kinase inhibitor 3-(4-methylphenylsulfonyl)-2-propenenitrile (Bay 11-7082) or the proteasome activity inhibitor Z-Leu-Leu-Leu-CHO (MG-132) inhibited the development of the BK B(1) receptor-sensitized contractile responses. Furthermore, pro-inflammatory cytokine interleukin-6 (IL-6) produced a leftward shift of the concentration-response curve to the BK B(1) receptor agonist, whereas anti-inflammatory cytokines interleukin-4 (IL-4) and tumor growth factor-beta1 (TGF-beta1) produced a rightward shift of the responses to des-Arg(9)-BK in our preparations. Taken together, these results point to NF-kappaB as a key intermediary in the activation of the expression of BK B(1) receptor-sensitized responses in HUV and support the role of inflammatory mediators in the modulation of this process.


Perfusion Assessment with the SPY System after Arterial Venous Reversal for Upper Extremity Ischemia.
The timing and pattern of reperfusion following arterial- venous reversal (AVR) in patients with terminal ischemia of an upper extremity is not well understood. The current case series describes the timing and pattern of reperfusion observed in patients with terminal upper extremity ischemia who underwent AVR and repeated postoperative indocyanine green (ICG) angiography between 2004 and 2009. For all included patients, the SPY Near-Infrared Perfusion Assessment System permitted visualization of ICG-labeled blood flow for 60-second sampling periods at scheduled postoperative time points; outflow and rate and amplitude of inflow were objectively quantified with SPY-Q Analysis Toolkit image analysis software. The series comprised 6 male patients (mean age, 46 years) who presented with upper extremity ischemia related to hypothenar hammer syndrome (n = 2), embolism with patent foramen ovale (n = 2), atherosclerosis (n = 1), and avulsion amputation of the thumb (n = 1); the patient with the avulsion amputation was diagnosed with thromboangiitis obliterans at the time of replantation. AVR was successful in all 6 patients. In 5 of 6 patients, ICG angiography and SPY-based visualization/quantification showed that venous outflow and arterial inflow gradually normalized (versus unaffected digits) between postoperative days (PODs) 0 and 3 and was maintained at long-term follow-up (≥3 months); for the patient who underwent thumb replantation, perfusion normalized between POD 3 and month 5 follow-up. AVR effectively reestablished blood flow in patients with terminal upper extremity ischemia. ICG angiography with SPY technology revealed that, in most cases, kinetic curves, timing, and patterns of perfusion gradually normalized over several PODs.


Exponential stabilization for sampled-data neural-network-based control systems.
This paper investigates the problem of sampled-data stabilization for neural-network-based control systems with an optimal guaranteed cost. Using time-dependent Lyapunov functional approach, some novel conditions are proposed to guarantee the closed-loop systems exponentially stable, which fully use the available information about the actual sampling pattern. Based on the derived conditions, the design methods of the desired sampled-data three-layer fully connected feedforward neural-network-based controller are established to obtain the largest sampling interval and the smallest upper bound of the cost function. A practical example is provided to demonstrate the effectiveness and feasibility of the proposed techniques.


Detection of methamphetamine and amphetamine in a single human hair by gas chromatography/chemical ionization mass spectrometry.
A detailed procedure of an extremely sensitive method for quantitation of methamphetamine and amphetamine in human hair by gas chromatography (GC)/chemical ionization (CI) mass spectrometry (MS) is presented. N-methylbenzylamine was used as an internal standard. The samples, after extraction with an organic solvent, were derivatized with trifluoroacetic anhydride before the GC/MS analysis. Quantitation was made with quasi-molecular ions of the derivatives by selected ion monitoring in the CI mode. The detection limit was about 10 pg in an injected volume. The high sensitivity enabled us to measure both stimulants in a single human hair in actual cases.


Protein-lipid interactions of the proteolipid c subunit of the Escherichia coli proton-translocating adenosinetriphosphatase.
Interactions between Escherichia coli membrane phospholipids and the hydrophobic c subunit of the F1F0 proton-translocating ATPase were characterized. Extraction of E. coli membranes with a neutral mixture of chloroform and methanol and subsequent separation steps produced several protein-containing fractions. The protein-containing fraction most soluble in organic solvents contained subunit c and a lipid fraction enriched in phosphatidylglycerol compared to total E. coli membrane phospholipids. Other ATPase subunits and some additional proteins extracted from the membranes by this procedure could be separated from the c subunit by subsequent extraction. The purified and delipidated c subunit contained fatty acids which were released upon treatment with boron trifluoride methanol. Furthermore, deleting and restoring the genes for the F0 subunits changed the composition of extractable membrane phospholipid and fatty acids, indicating that the F0 plays a significant structural role in the membrane.


Dermatologist-diagnosed skin diseases among immigrant Latino poultry processors and other manual workers in North Carolina, USA.
Immigrant Latino workers represent an expanding workforce in rural areas of the USA, where their employment is concentrated in occupations such as poultry processing that entail chemical, infectious, and mechanical skin exposures. Occupation-related skin illnesses in this vulnerable population are not well characterized. This study was designed to describe the prevalences of skin diseases among immigrant Latino poultry processors and other manual workers in North Carolina. Community-based sampling was used to recruit 742 immigrant Latino workers, 518 of whom underwent a physical examination supervised by a board-certified dermatologist. The presence or absence of skin disease on the face, neck, arms, hands, and feet was recorded. Workers ranged in age from 18 years to 68 years. Slightly over half of the sample were male (52.6%). Poultry workers represented 55.8% of the study sample. Infectious skin diseases were the most common diagnosis, present in 52.3% of workers. Inflammatory skin diseases were present in 28.2% and pigmentary disorders in 21.8% of workers. The most common skin conditions were tinea pedis (37.6%), onychomycosis (31.9%), scars (13.7%), acne (11.8%), and melasma (9.3%). Age, sex, first language, and work as a poultry processor accounted in part for the prevalence of these diseases. Several skin diseases are highly prevalent in immigrant Latino workers and may relate to work environment. These may impair the quality of life of these workers and predispose them to further illness.


State policy and health disparities: an examination of the impact of state offices of minority health.
For over two decades, a concerted effort has been underway to tackle health disparities. State Offices of Minority Health (OMH) have led efforts in data collection, training, and policy development. Yet, little evidence exists regarding the effectiveness of these efforts. I address this dearth of knowledge by examining the impact of state Offices of Minority Health on Black infant mortality rates. I perform a longitudinal regression analysis controlling for political, economic, and policy variables. I find that state OMHs are associated with a decrease in Black infant mortality rates. Furthermore, when Medicaid spending is low, the implementation of a state OMH decreases Black infant mortality over time. As Medicaid spending increases, however, the effect diminishes. State OMHs and Medicaid are important tools to decrease Black infant mortality rates. States that invest relatively little in health care for the poor should consider increasing investments in their Offices of Minority Health.


Tin Nanodots Encapsulated in Porous Nitrogen-Doped Carbon Nanofibers as a Free-Standing Anode for Advanced Sodium-Ion Batteries.
Ultrasmall Sn nanodots (1-2 nm) are homogeneously encapsulated in porous N-doped carbon nanofibers using a simple and scalable electrospinning method. The composite nanofibers weave into flexible free-standing membrane and can be directly used as binder- and current collector-free anode for Na-ion batteries, exhibiting excellent electrochemical performance with high reversible capacity, exceptional rate capability, and ultralong cycle life.


Ion Pre-Embedding Engineering of δ-MnO2 for Chemically Self-Charging Aqueous Zinc Ions Batteries.
Aqueous zinc ion batteries (ZIBs), especially those with self-charging properties, have been promisingly developed in recent years. Yet, most inorganic materials feature high redox potential, which limit their development in the self-charging field. To achieve this target, by pre-embedding potassium ions into δ-MnO2 to reduce the energy barrier in oxygen adsorption, the first application of MnO2 in self-charging ZIBs is realized. The design features a facile two-electrode configuration with no excessively complex component to allow for energy storage and conversion. Due to the voltage difference between the oxygen in the air and the discharge products, a redox reaction can be carried out spontaneously to realize the self-charging process. After the chemical self-charging process, the Zn-K0.37 MnO2 ·0.54H2 O/C cell achieves an open circuit voltage of around 1.42 V and a discharge capacity of 201 mAh g-1 , reflecting the promising self-charging capability. Besides, the chemically self-charging ZIBs operate well in multiple modes of constant current charge/discharge/chemical charging. And decent cycling capability can also be achieved at extreme temperatures and high mass loading. This work promotes the development of ZIBs and further broadens the application of inorganic metal oxides in the self-charging systems.


Interfacial Engineering of NiO/NiCo2O4 Porous Nanofibers as Efficient Bifunctional Catalysts for Rechargeable Zinc-Air Batteries.
To meet the crucial demand of regenerative Zn-air (ZA) batteries, low cost, highly efficient, and durable electrocatalysts for the oxygen evolution reaction (OER) and oxygen reduction reaction (ORR) are needed to replace the noble metal. Herein, porous NiO/NiCo2O4 nanofibers with superior electrocatalytic performance are synthesized by a facile electrospinning strategy with precursor transition metal salts in nonstoichiometric ratio, which confers the heterostructured NiO/NiCo2O4 with abundant interface-related active sites and electronic transmission channels. Density functional calculation results reveal the chemical bonds easily form between NiO and NiCo2O4 to facilitate the charge transfer, while X-ray absorption fine spectroscopy and X-ray photoelectron spectroscopy results demonstrate there are abundant Ni3+ and Co3+ species in NiO/NiCo2O4 due to the interfacial engineering. As a result, the NiO/NiCo2O4 porous nanofibers exhibit highly efficient and durable performances of OER and ORR in KOH solution, including a lower overpotential of 357 mV at 10 mA cm-2 (OER) and half-wave potential of 0.73 V (ORR) than that of the individual. What's more, the NiO/NiCo2O4-based ZA battery displays excellent specific capacities of 814.4 mA h g-1, and good cycling stability of 175 h. Additionally, the flexible ZA battery displays a long cycling life of 14 h and decent flexibility. This work shows that construction of the heterostructure could provide a feasible method to optimize their electrocatalytic performance and make them widely used in power source devices.


Macromolecular synthesis in wing discs of Spodoptera mauritia Boisd: effects of a juvenile hormone analogue.
Last instar larvae of S. mauritia treated topically on day 0, day 1, day 2 and day 3 with a daily (dose of 25 microg juvenile hormone analogue (JHA) moulted into supernumerary larvae. The imaginal discs of the supernumerary larvae especially those of mouthparts and thoracic appendages showed pupal characteristics. However the wing discs, which showed only partial differentiation, were uneverted and highly tanned. In an effort to provide an explanation to this anomaly the RNA, DNA and protein profile in the wing discs of supernumerary larvae were studied. Quantitative analysis of DNA, RNA and protein showed a considerable increase in the amount of DNA and protein and a decline in RNA level. SDS-PAGE analysis of wing disc proteins of JHA treated larvae showed a reduction in the expression of many major proteins that were predominant in the wing discs of control larvae. The results suggest that JHA induced inactivation of genes involved in the synthesis of proteins needed for evagination process may be responsible for the formation of uneverted, partially differentiated pupal wing discs in supernumerary larvae.


EFA (9-beta-D-erythrofuranosyladenine) is an effective salvage agent for methylthioadenosine phosphorylase-selective therapy of T-cell acute lymphoblastic leukemia with L-alanosine.
The deficiency of methylthioadenosine phosphorylase (MTAP) in T-cell acute lymphoblastic leukemia (T-ALL) and other cancers, while constitutively expressed in normal cells, allows for selective therapy using L-alanosine, an inhibitor of de novo AMP synthesis. We demonstrate that MTAP- T-ALL cells obtained at relapse are as sensitive to L-alanosine toxicity as diagnosis samples. The therapeutic index of L-alanosine can be increased by the use of a MTAP substrate, which protects MTAP+ normal cells. Since MTAP substrates MTA and 5'deoxyadenosine are prone to toxicities associated with adenosine, we synthesized and evaluated a potentially nontoxic MTAP substrate, 9-beta-D-erythrofuranosyladenine (EFA). The cytotoxicity of EFA to hematopoietic progenitors erythroid burst-forming units (BFU-Es) and granulocyte-macrophage colony-forming units (CFU-GMs) was at least 26- to 41-fold less than that of MTA. In addition, EFA selectively rescued MTAP+ MOLT-4 cells from L-alanosine toxicity at 25 microM with negligible toxicity even at 100 microM. As for MTA, significant, albeit incomplete, rescue was achieved at 12.5 microM, but higher concentrations were toxic. EFA at 20 microM or less rescued primary MTAP+ T-ALL cells and normal lymphocytes from L-alanosine toxicity. Collectively, these data indicate that EFA is an effective agent for salvaging MTAP+ cells from L-alanosine toxicity and is superior to MTA due to lower cytotoxicity.


Reduced Long-Term Risk of Aortic Aneurysm and Aortic Dissection Among Individuals With Type 2 Diabetes Mellitus: A Nationwide Observational Study.
No studies have examined long-term risks for aortic aneurysm (AA) and aortic dissection (AD) or mortality after AA or AD hospitalization among patients with type 2 diabetes mellitus (T2DM). In this observational cohort study, we linked data for patients with T2DM in the Swedish National Diabetes Register, and 5 individually matched population-based control subjects (CSs) without diabetes mellitus (on the basis of sex, age, and county), to other national databases to capture hospitalizations and death. We examined the risk of hospitalization for AA and AD, as well as mortality risk after AA and AD using Kaplan-Meier curves and Cox regression hazards models. Data on 448 319 patients with T2DM and 2 251 015 CSs were obtained between 1998 and 2015. Mean follow-up time was 7.0 years for the T2DM group and 7.2 years for the CS group. Patients with T2DM had a relative risk reduction of 28% (hazard ratio, 0.72; 95% confidence interval, 0.68-0.76; P<0.0001) for AA and a 47% relative risk reduction (hazard ratio, 0.53; 95% confidence interval, 0.42-0.65; P<0.0001) for AD compared with CSs. Patients with T2DM had a relative risk reduction of 12% (hazard ratio, 0.88; 95% confidence interval, 0.82-0.94; P<0.0001) for mortality after hospitalization for AA, and unaltered risk (hazard ratio, 1.07; 95% confidence interval, 0.85-1.34; P=0.5859) for mortality after AD, up to 2 years compared with CSs. Patients with T2DM had significantly reduced risks of AA and AD as well as reduced risk of mortality after hospitalization for AA, compared to CS. Data suggest that glycated cross-links in aortic tissue may play a protective role in the progression of aortic diseases among patients with T2DM.


Estimating temporary populations.
The difficulty of tracking temporary short-term population movements (commuting, seasonal visitation, convention and business travel) is examined, with a focus on Hawaiian statistician Robert Schmitt's work. The author finds that "Schmitt's contributions toward a methodology for estimating daytime populations were important because this approach utilized data sources that were widely available for small areas on at least an annual basis. Consequently, this approach could be used for frequent updates of the estimates, for many areas and at relatively little cost.... The major drawback of the approach is the lack of solid data on temporary residents to serve as larger-area control totals and as a historical base for small-area estimates." The geographical focus is on the United States, particularly Hawaii.


Parity and parents' health in later life: the gendered case of Ismailia, Egypt.
We investigate the relationship between reproduction and functional health in later life among women and men in the resource-poor and gender-stratified setting of Ismailia governorate, Egypt. Analyses of survey data collected in 2003 show a statistically significant positive association between parity and difficulty with activities of daily living (ADLs), controlling for demographic and socio-economic factors and other co-morbid conditions. We also find that the number of daughters (but not sons) is associated with worse physical functioning, and this association is more pronounced for older fathers than for older mothers. Our results indicate that both biological and social pathways link fertility and later-life health in this context, and that prescribed familial roles may underlie the differential impact of sons and daughters on the health of mothers and fathers in later life.


Projection pursuit nonparametric regression applied to field counts of the aphid Macrosiphum euphorbiae (Homoptera: Aphididae) on tomato crops in greenhouses.
The number of plants that sampling requires in aphid population studies often exceeds one hundred. Thus, only quick and nondestructive methods can be used to sample this pest in a reasonable time interval. We propose a visual method for estimating the density of the aphid Macrosiphum euphorbiae (Thomas) on tomato plants reared in greenhouses. After approximately 1min of visual observation plants can be assigned to abundance classes, the boundaries of which are roughly the powers of square root 10. Precise counts were collected simultaneously on sets of reference plants from the same greenhouse. Projection pursuit nonparametric regression was then used to provide unbiased estimates of aphid densities from the abundance classes and several easily gathered explanatory variables. The robustness of the method was evaluated by testing the models on the complementary data sets from plants in which the aphid densities were precisely counted. In both single and twin-row cultural conditions, for the reference and complementary data sets, the order of magnitude of the error was less than one class rank per plant. The investigation time was reduced by approximately 10-fold compared with the exact counting method. This easy-to-teach field method could be useful in large-scale population surveys and for optimizing integrated pest management strategies.


In vitro evaluation of an asthma dosing device: the smart-inhaler.
Monitoring devices attached to pressurised metered dose inhalers provide an important objective measurement of patient adherence with asthma medications in clinical and research settings. The Smart-inhaler is a relatively new device that has not been previously validated. This study examines the accuracy of the Smart-inhaler in a bench-top experiment and compares it with a previously validated device, the Doser. Ten Smart-inhalers and five Dosers were actuated twice on two occasions per day for 30 days (120 doses). Six Smart-inhalers were also actuated 30 times in rapid succession to examine the ability of the Smart-inhaler to detect "dumping". Five Smart-inhalers failed to detect the first one or two doses. However, when the aerosol canister was placed more firmly in the device, actuating the device in the process, the following two doses were recorded accurately in all ten devices. Otherwise all ten Smart-inhalers and five Dosers recorded all actuations faithfully and there were no spurious recordings. The six Smart-inhalers recorded all 30 doses delivered in rapid succession. The Smart-inhaler and Doser are both highly accurate at measuring actuated doses and no spurious doses were recorded in an in vitro setting.


The joint association of physical activity and sedentary behavior with health-related quality of life among children and adolescents in Mainland China.
The objective of this study was to investigate the joint association of physical activity (PA) and sedentary behavior (SB) with health-related quality of life (HRQoL) among children in Mainland China. Children were randomly recruited from primary, junior, and senior high schools (graders 4-12) in Nanjing municipality of China in this cross-sectional survey in 2018. The outcome variable, HRQoL, was assessed using the validated Chinese version of Child Health Utility 9D (CHU9D-CHN) instrument. PA and SB were measured using a validated Physical Activity Scale and Food Frequency Questionnaire for Chinese school-aged children. The associations of PA and SB with HRQoL were assessed using mixed-effects linear regression models and reported as mean difference (MD) and 95% confidence interval (CI). Totally, 4,388 participants completed the survey (response rate = 97.6%). After adjustment for potential confounders and class-level clustering effects, relative to those with insufficient PA and prolonged SB, students with insufficient PA and shortened SB (MD = 0.054, 95%CI = 0.018, 0.089), or children with sufficient PA and prolonged SB (MD = 0.034, 95%CI = -0.030, 0.098), or students with sufficient PA and shortened SB (MD = 0.083, 95%CI = 0.045, 0.120), respectively, reported increased HRQoL scores. PA was positively associated with HRQoL, and SB was in negative relation to HRQoL. Furthermore, sufficient PA and shortened SB might exert additive influence on HRQoL among children and adolescents in China. This study has public health implications that PA promotion and SB reduction are encouraged to be considered simultaneously for the purpose to maximally improve HRQoL in population-based behavior intervention campaigns among children and adolescents.


Regional variation in undulatory kinematics of two hammerhead species: the bonnethead (Sphyrna tiburo) and the scalloped hammerhead (Sphyrna lewini).
Hammerhead sharks (Sphyrnidae) exhibit a large amount of morphological variation within the family, making them the focus of many studies. The size of the laterally expanded head, or cephalofoil, is inversely correlated with pectoral fin area. The inverse relationship between cephalofoil and pectoral fin size in this family suggests that they might serve a complementary role in lift generation. The cephalofoil is also hypothesized to increase olfaction, electroreception and vision; however, little is known about how morphological variation impacts post-cranial swimming kinematics. Previous studies demonstrate that the bonnethead and scalloped hammerhead have significantly different yaw amplitude, and we hypothesized that these species utilize varied frequency and amplitude of undulation along the body. We analyzed video of free-swimming sharks to examine kinematics and 2D morphological variables of the bonnethead and scalloped hammerhead. We also examined the second moment of area along the length of the body and over a size range of animals to determine whether there were shape differences along the body of these species and whether those changed over ontogeny. We found that both species swim with the same standardized velocity and Strouhal number, but there was no correlation between two-dimensional morphology and swimming kinematics. However, the bonnethead has a dorso-ventrally compressed anterior trunk and undulates with greater amplitude, whereas the scalloped hammerhead has a laterally compressed anterior trunk and undulates with lower amplitude. We propose that differences in cross-sectional trunk morphology account for interspecific differences in undulatory amplitude. We also found that for both species, undulatory frequency is significantly greater in the anterior body compared with all other body regions. We hypothesize that the bonnethead and scalloped hammerhead swim with a double oscillation system.


Breastfeeding a baby with a cleft palate: a case report.
A case report is presented on the experience of breastfeeding a baby with a cleft palate. The importance of breastfeeding for the baby and the mother is discussed as well as the importance of support from health care professionals. Problems are described relating to (a) the long term maintenance of lactation by exclusive breast pumping; and (b) the lack of information available on feeding techniques and devices helpful in breastfeeding prior to and following palate repair. Practical suggestions are proposed for expressing and feeding expressed milk to a baby with a cleft palate.


Multiple spatially specific enhancers are required to reconstruct the pattern of Hox-2.6 gene expression.
Murine Hox genes are organized into four clusters that share many features with the homeotic clusters of Drosophila. This evolutionary conservation and the clear relationships between the position of a gene within a cluster and its expression pattern have led to the suggestion that the structure of the cluster is essential for proper regulation. Using a Hox-2.6-lacZ reporter gene in transgenic mice we have shown that the overall expression pattern of the endogenous Hox-2.6 gene can be reconstructed when it is isolated from the complex. The transgene was expressed in the proper tissues, with the correct spatial distribution and temporal pattern. Furthermore, direct comparison by in situ hybridization revealed that the levels of transgene expression are similar to those of the endogenous gene. This has allowed us to define three elements that regulate particular aspects of the Hox-2.6 pattern, two of which act as spatially specific enhancers. One enhancer, region A, directed expression only in the neural tube, whereas the other, region C, specified the majority of the Hox-2.6 pattern. Both were also capable of imposing the correct boundaries of expression on heterologous promoters. The definition of such elements will allow the characterization of the trans-acting factors that mediate spatial regulation in the mammalian embryo.


Visual locomotion scoring in the first seventy days in milk: impact on pregnancy and survival.
Our hypotheses were that cows classified as lame during the first 70 d in milk have more days from calving to conception and a greater hazard of dying or being culled compared with cows that were not classified as lame. Our objective was to estimate the detrimental effects of lameness on calving-to-conception interval and hazard of dying or being culled in lactating Holstein cows. Data were collected from 5 dairy farms located in upstate New York from November 2004 to June 2006. The design was a prospective observational cohort study. Cows were assigned a visual locomotion score (VLS) using a 5-point scale: 1 = normal, 2 = presence of a slightly asymmetric gait, 3 = the cow clearly favored 1 or more limbs (moderately lame), 4 = severely lame, to 5 = extremely lame (nonweight-bearing lame). In total 1,799 cows were enrolled. In 2 alternative categorizations, cows were considered lame if at least 1 VLS was > or =3 during the first 70 d in milk, and if at least 1 VLS was > or =4 for the same period they were considered lame. Lameness (VLS > or =3) was detected at least once in 26.5, 54.2, 33.9, 51.8, and 39.3% of all cows in farms 1 to 5, respectively. The hazard ratio of being detected pregnant was 0.85 for lame cows (VLS > or =3) vs. nonlame cows; hence, lame cows were at a 15% lower risk of pregnancy than nonlame cows. When lameness was redefined as VLS > or =4, the hazard ratio of been detected pregnant was 0.76 for lame cows vs. cows with VLS <4. Lameness increased the hazard ratio of culling/death, 1.45 and 1.74 for VLS > or =3 and VLS > or =4, respectively, vs. cows with VLS <3 and VLS <4, respectively. In summary, lameness significantly decreased the hazard of pregnancy and increased the hazard of culling/death. The detrimental effects were amplified when considering only severely lame and non-weight-bearing cows.


The chelatable iron pool in living cells: a methodically defined quantity.
A very small, predominantly cytosolic pool of iron ions plays the central role in the cellular iron metabolism. It links the cellular iron uptake with the insertion of the metal in iron storage proteins and other essential iron-containing molecules. Furthermore, this transit ('labile') pool is essentially involved in the pathogenesis of a number of diseases. Due to its high physiological and pathophysiological significance, numerous methods for its characterization have been developed during the last five decades. Most of these methods, however, influence the size and nature of the transit iron pool artificially, as they are not applicable to viable biological material. Recently, fluorescence spectroscopic methods for measurements within viable cells have become available. Although these methods avoid the artifacts of previous methods, studies using fluorescent iron indicators revealed that the 'intracellular transit iron pool', which is methodically assessed as 'chelatable iron', is substantially defined by the method and/or the iron-chelating indicator applied for its detection, since the iron ions are bound to a large number of different ligands in different metabolic compartments. A more comprehensive characterization of the nature and the role of the thus not uniform cellular transit iron pool therefore requires parallel employment of different indicator molecules, which clearly differ in their intracellular distribution and their physico-chemical characteristics.


Heat shock protein 32 in human peripheral blood mononuclear cells: effect of aging and inflammation.
The purpose of the present study was to assess the influence of age and acute infection on the production of Hsp32 in human peripheral blood cells, using flow cytometry. Thirty-five controls and 31 patients with acute infection participated. We found that the age and inflammatory status correlated positively with Hsp32 levels in both heat shocked (HS) and non-HS monocytes and lymphocytes. In addition, the HS response of Hsp32 was different in these peripheral blood cells; whereas HS exerted an up-regulation in the levels of Hsp32 in monocytes, a significant decrease in Hsp32 levels was noticed for lymphocytes. We found significant relationships between circulating C-reactive protein as well as interleukin-6 and the levels of Hsp32 in cells. We conclude that Hsp32 is up-regulated in the elderly as well as in individuals with inflammation, and that the HS response of Hsp32 is different in monocytes as compared to lymphocytes.


Metformin and leucine increase satellite cells and collagen remodeling during disuse and recovery in aged muscle.
Loss of muscle mass and strength after disuse followed by impaired muscle recovery commonly occurs with aging. Metformin (MET) and leucine (LEU) individually have shown positive effects in skeletal muscle during atrophy conditions but have not been evaluated in combination nor tested as a remedy to enhance muscle recovery following disuse atrophy in aging. The purpose of this study was to determine if a dual treatment of metformin and leucine (MET + LEU) would prevent disuse-induced atrophy and/or promote muscle recovery in aged mice and if these muscle responses correspond to changes in satellite cells and collagen remodeling. Aged mice (22-24 months) underwent 14 days of hindlimb unloading (HU) followed by 7 or 14 days of reloading (7 or 14 days RL). MET, LEU, or MET + LEU was administered via drinking water and were compared to Vehicle (standard drinking water) and ambulatory baseline. We observed that during HU, MET + LEU resolved whole body grip strength and soleus muscle specific force decrements caused by HU. Gastrocnemius satellite cell abundance was increased with MET + LEU treatment but did not alter muscle size during disuse or recovery conditions. Moreover, MET + LEU treatment alleviated gastrocnemius collagen accumulation caused by HU and increased collagen turnover during 7 and 14 days RL driven by a decrease in collagen IV content. Transcriptional pathway analysis revealed that MET + LEU altered muscle hallmark pathways related to inflammation and myogenesis during HU. Together, the dual treatment of MET and LEU was able to increase muscle function, satellite cell content, and reduce collagen accumulation, thus improving muscle quality during disuse and recovery in aging.


Mechanisms from Academic Stress to Subjective Well-Being of Chinese Adolescents: The Roles of Academic Burnout and Internet Addiction.
Academic stress is commonly known to affect adolescents' subjective well-being, but the influencing mechanisms are rarely investigated in the Chinese context. This study aims to investigate the psychological and behavioral factors operating as pathways between academic stress and adolescents' subjective well-being. A multi-stage cluster random sampling is used to select 1043 adolescents from junior and senior high schools in Jinhu County, Jiangsu Province, China (mean age=14.98 years; 51.1% boys). Structural equation modeling is used to test the direct and indirect effects. Academic stress is significantly correlated with adolescents' subjective well-being after controlling for gender, grade, hukou, and socioeconomic status. In addition to partially mediating the link between academic stress and subjective well-being, academic burnout and Internet addiction can also operate as chain mediators in this mechanism. Adolescents' subjective well-being shows significant gender disparities, with boys having a greater degree of subjective well-being than girls. Father's income is found to have a significant positive association with adolescents' subjective well-being. The results indicate that academic stress is a significant predictor of academic burnout, which in turn points to a positive association with Internet addiction, thereby explaining low levels of adolescents' subjective well-being. The present study develops current knowledge and expands our understanding of the underlying mechanisms by which academic stress influences adolescents' subjective well-being. This can also illuminate the practical ramifications for policymakers and social workers to mitigate academic-related stress and burnout, prevent Internet addiction, and ultimately promote the well-being of adolescent students.


New Frontiers in the Proteome Research Quantitative Proteomics.
In the past years, proteome research has achieved very exciting advances. The automation of 2DE-MS approach and the use of multidimensional liquid chromatography (LC) and tandem mass spectrometry (MS/MS) have overcome many disadvantages of two-dimensional gel electrophoresis. The stable isotope labeling and the isotope-coded affinity tags (ICAT) strategy provided an ideal method for accurately quantitating the low copy number proteins which play a key role in cells or tissues. At the same time, the research of the quantitative proteomics has been improved greatly with the development of the protein chip technology. Recent advances of the research in the quantitative proteomics and the related technologies are reviewed.


Mycobacterium tuberculosis infection of a tophaceous pseudogout nodule.
Musculoskeletal infections are uncommon complications of monosodium urate and calcium pyrophosphate dihydrate (CPPD) crystal deposition disease, and frequently involve gram positive and negative organisms. Tumoral calcinosis (tophaceous pseudogout) is a rare manifestation of CPPD deposition disease. We describe a highly unusual case of an infection by Mycobacterium tuberculosis (TB) of a tophaceous pseudogout nodule in a patient with endstage renal disease. The highly destructive nature of this case of combined CPPD arthropathy and musculoskeletal TB underscores the urgency of diagnosing this infection in susceptible patients from countries with high prevalence rates of TB infection.


Clinical characteristics and prognosis of Neuro-Behçet's disease.
Neuro-Behçet's disease (NBD) is a rare manifestation of Behçet's disease (BD) and may cause severe disability. The aim of this study was to evaluate the treatment response in patients with NBD and to investigate the parameters that may influence the prognosis of the disease in patients with severe to mild-moderate disability. The files of 60 patients admitted to our outpatient clinic for NBD between January 2007 and June 2014 were retrospectively reviewed. We compared the BD duration, time to NBD, NBD type and course, clinical findings of BD, functional neurological system involvement, localization of lesions on brain MRI, and all the medications between the severe and mild-moderate disability groups. The mean time to the onset of NBD was significantly longer (17.8±4.6 years) and the mean age was significantly higher (50.25±9.1 years) in patients with severe disability than in those with mild-moderate disability (7.5±8.0 years and 37.5±10.9 years; p=0.01 and p=0.03, respectively). Moreover, hemispheric involvement was significantly associated with severe disability (p=0.006). No difference was found with regard toother investigated parameters between the groups. We believe that severe neurological disability may be associated with older age at the onset of NBD or longer time to NBD and hemispheric lesions on brain MRI. However, our results should be cautiously evaluated with further research.


TDM-guided therapy with daptomycin and meropenem in a morbidly obese, critically ill patient.
To describe a case of severe cellulitis, successfully treated with high-dose daptomycin plus continuous infusion meropenem, in a patient with morbid obesity and renal failure, in whom drug exposure over time was optimized by means of real-time therapeutic drug monitoring (TDM). A 63-year-old man with morbid obesity (body mass index 81.6 kg/m²) and renal failure was admitted to the emergency department because of severe cellulitis. The patient had an admission Laboratory Risk Indicator for Necrotizing Fasciitis score of 9, and broad-spectrum antimicrobial therapy with daptomycin and meropenem was started. Because of rapidly changing renal function, dosage adjustments were guided by an intensive program of TDM (daptomycin ranging from 1200 mg every 48 hours over 30 minutes to 1200 mg every 36 hours over 30 minutes; meropenem ranging from 0.25 g every 8 hours over 6 hours to 500 mg every 4 hours by continuous infusion). Clinical response was observed within 72 hours. However, a sudden increase of serum creatine kinase (SCK) raised questions about the need for discontinuation of daptomycin. The drug concentrations were not toxic; therefore, we decided to continue therapy. Significant clinical improvement, with SCK normalization, was observed within a few days. Antimicrobial therapy was switched on day 29 to amoxicillin/clavulanate plus levofloxacin, and then discontinued at discharge on day 53. High-dose daptomycin plus continuous infusion meropenem may ensure adequate empiric antimicrobial coverage in patients with possible early necrotizing fasciitis. However, in patients with morbid obesity and changing renal function, significant challenges may arise because of the hydrophilic nature of these drugs and the inaccuracy of standard methods of estimating renal function. Real-time TDM may represent an invaluable approach in optimizing drug exposure with high-dose daptomycin plus continuous infusion meropenem in patients with severe cellulitis, morbid obesity, and changing renal function.


Spina Ventosa of the Right Index Finger in an Adult Indian Female With No Pulmonary Involvement: A Rare Case.
Tubercular involvement of small bones is a rare clinical condition. Often, the disease is associated with pulmonary involvement. Isolated cases of spina ventosa in adults with no pulmonary seeding or any history of tuberculosis or trauma are relatively infrequent occurrences. We report a case of a 22-year-old immunocompetent Indian female who presented with complaints of a swollen right index finger. A detailed clinical workup supported by radiographs and serological tests established the diagnosis as primary tubercular dactylitis of the right index finger. She was managed with anti-tubercular drugs.


Azacrown-calixpyrrole isosteres: receptors and sensors for anions.
Calix[4]pyrroles (CPs) and polyammonium azacrowns (ACs) are well-known receptors for anions. CPs bind anions by directional hydrogen bonds that do not always work well for aqueous analytes. The positive charge in polyammonium ACs allows for a stronger but non-directional anion-ammonium electrostatic attraction but lack selectivity. Bridging the gap between CPs and ACs could increase affinity and potentially preserve the selectivity of anion binding. We have synthesized a flexible calixpyrrole-azacrown near isosteric receptor and incorporated an environmentally sensitive dansyl fluorophore to enable fluorescence measurements. Anion binding was evaluated using NMR and fluorescence titrations. The isosteric receptor shows a strong affinity for aqueous phosphates and phosphonates (Na+ salts) in the order HAsO42- > H2PO4- > H2P2O72- > glyphosate2- > AMP- > methylphosphonate- ≫ ADP2- or ATP3- but does not bind halides. This is in stark contrast to CP which shows a strong preference for halides over oxyanions. The anion binding by the new receptor was accompanied by analyte-specific changes in fluorescence intensity and spectral width and by a wavelength shift. These parameters were used in qualitative and quantitative sensing of aqueous anions. By applying machine-learning algorithms, such as linear discriminant analysis and support vector machine linear regression, this one sensor can differentiate between 10 different analytes and accurately quantify herbicide glyphosate and methylphosphonate, a product of sarin, soman or cyclosarin hydrolysis. In fact, glyphosate can be quantified even in the presence of competing anions such as orthophosphate (LODs were ≤ 1 μM).


[A Case of Rectal Cancer with Multiple Endocrine Neoplasia Type 2].
A 63-year-old man with multiple endocrine neoplasia type 2(MEN2)was admitted to the hospital because of positive fecal occult blood tests. Colonoscopy revealed a 50mm type 2 tumor at the rectum, which was diagnosed as an adenocarcinoma based on histology. Since there was no apparent distant metastasis, laparoscopy-assisted low anterior resection with regional lymph node dissection was performed. The final diagnosis was pT3, pN0, pM0, pStage II . Almost all patients with MEN2 have RET mutations, and they are resistant to EGFR inhibitors. Those who have thyroid cancer with RET mutations are often given a RET kinase inhibitor. In this case, if the patient develops recurrent rectal cancer, it warrants checking for RET mutations and using a multi-kinase inhibitor.


Inhibition of DNA replication by berenil in plasmids containing Poly(dA)poly(dT) sequences.
The effect of berenil on plasmid DNA replication was studied on pBR322-derived plasmids containing poly(dA)poly(dT) sequences. In comparison to the parental plasmid pBR322, plasmid pKH47 harboring 100 bp of poly(dA)poly(dT) at the PvuII site showed a decrease in plasmid yield in the presence of berenil. This effect was also observed in pVL26, a related plasmid in which the location of the poly(dA)poly(dT) region had been shifted to the EcoRV site in pBR322. [(3)H]Thymidine incorporation experiments indicated that DNA synthesis may be affected in these plasmids in the presence of the drug. Bromodeoxyuridine incorporation experiments coupled to Cs(2)SO(4) equilibrium density gradient centrifugation indicated that the lower plasmid yield was due to an inhibition of DNA replication by berenil. We have also found that berenil induces DNA degradation in plasmids containing the homopolymer. Our studies strongly suggest that the effect of berenil on plasmid replication and DNA stability results from its binding to the poly(dA)poly(dT) region present in these plasmids. Moreover, we have found a correlation between the position of the poly(dA)poly(dT) region and this inhibitory effect. Thus, plasmid pKH47, containing the poly(dA)poly(dT) region most proximal to the origin of pBR322 replication, was most severely affected.


[Efficacy of a new antisecretory agent (40 749 RP) on human gastric secretion induced by a meal (intragastric titration)].
An antisecretory drug of a new series, 40 749 RP, without anticholinergic or H2 receptor antagonist activities, was tested on meal-induced gastric acid secretion in 6 healthy volunteers. Gastric acid secretion and emptying of liquid were measured using intragastric titration. Oral dosages tested were 1, 2 and 4 mg/kg versus placebo. Inhibitions obtained were dose-related and expressed in percentage of the placebo values: 36 +/- 10 p. 100 for 1 mg/kg; 51 +/- 13 p. 100 for 2 mg/kg and 83 +/- 5 p. 100 for 4 mg/kg. Statistically significant correlation (p less than 0.001) was observed between maximal blood concentration of 40 749 RP and the percentage of secretory inhibition during the 90 min of the test. No change in gastrin response or in gastric emptying was observed whatever the dose.


The Manipulation of Pace within Endurance Sport.
In any athletic event, the ability to appropriately distribute energy is essential to prevent premature fatigue prior to the completion of the event. In sport science literature this is termed "pacing." Within the past decade, research aiming to better understand the underlying mechanisms influencing the selection of an athlete's pacing during exercise has dramatically increased. It is suggested that pacing is a combination of anticipation, knowledge of the end-point, prior experience and sensory feedback. In order to better understand the role each of these factors have in the regulation of pace, studies have often manipulated various conditions known to influence performance such as the feedback provided to participants, the starting strategy or environmental conditions. As with all research there are several factors that should be considered in the interpretation of results from these studies. Thus, this review aims at discussing the pacing literature examining the manipulation of: (i) energy expenditure and pacing strategies, (ii) kinematics or biomechanics, (iii) exercise environment, and (iv) fatigue development.


Comparative analysis of the microbial community and nutritional quality of sufu.
Sufu is a type of fermented food with abundant nutrients and delicious taste. It is made from the fermentation of tofu by various microorganisms. In this study, three types of sufu were prepared through natural fermentation: (NF), single-strain fermentation (SF), and mixed-strain fermentation (MF). Microbial species, amino acids, and fatty acids were identified to investigate dynamic changes in nutritional quality and microbial flora in sufu. The results showed that the number of microbial species in NF sufu was the highest (n = 284), whereas that in SF sufu was the lowest (n = 194). Overall, 153 microbial species were found in all three types of sufu. Relative abundance analysis also revealed that Tetragonococcus, Bacillus, Acinetobacter, and Staphylococcus were the main bacteria in sufu. However, there was a large number of harmful bacteria such as Enterococcaceae in NF sufu. The levels of various nutrients were low in SF sufu, whereas the contents of protein and soy isoflavones were higher in NF and MF sufu. Seventeen kinds of amino acids were detected, comprising seven essential amino acids and ten other amino acids. The contents of essential amino acids and essential fatty acids were higher in MF sufu than the other two types, resulting in its high nutritional value. The sufu produced through the three fermentation methods differed significantly (p < .05) in terms of microbial flora and nutritional quality.


A highly efficient genetic transformation system for broccoli and subcellular localization.
Agrobacterium-mediated genetic transformation has been widely used for the identification of functional genes and regulatory and developmental mechanisms in plants. However, there are still some problems of low genetic transformation efficiency and high genotype dependence in cruciferous crops. In this study, broccoli, a worldwide Brassica crop, was used to investigate the effects of genotype, explant type, concentration of hygromycin B used during seedling selection, overexpression vector type, RNAi and CRISPR/cas9 on the genetic transformation efficiency. At the same time, two vectors, PHG-031350 and PHG-CRa, were used for subcellular localization of the glucoraphanin synthesis-related gene FMOGS-OX5 and clubroot resistance gene by a PEG-Ca2+-mediated transient transformation system for broccoli protoplasts. Finally, the Agrobacterium-mediated genetic transformation system of broccoli was optimized and improved. This study showed that hypocotyl explants are more suitable for Agrobacterium-mediated transgene and CRISPR/Cas9 gene editing of broccoli. In contrast to previous studies, we found that 5 mg/L hygromycin B was more advantageous for the selection of resistant broccoli sprouts, and genotype 19B42 reached the highest transformation rate of 26.96%, which is higher than that in Brassica oleracea crops. In addition, the inbred line 19B42 successfully achieved high genetic transformation of overexpression, RNAi and CRISPR/Cas9 vectors; thus, it is powerful recipient material for the genetic transformation of broccoli. Subcellular localization proved that the glucoraphanin metabolism-related gene Bol031350 and clubroot resistance gene CRa were both expressed in the cytoplasm and nucleus, which provided a scientific basis for studying the regulation of glucosinolate metabolism and clubroot resistance in cruciferous crops. Therefore, these findings will provide new insight into the improvement of the genetic transformation and molecular breeding of Brassica oleracea crops.


SPARC Metrics Provide Mobility Smoothness Assessment in Oldest-Old With and Without a History of Falls: A Case Control Study.
Aging-related neuromuscular and neurocognitive decline induces unsmooth movements in daily functional mobility. Here, we used a robust analysis of linear and angular spectral arc length (SPARC) in the single and dual task instrumented timed up-and-go (iTUG) test to compare functional mobility smoothness in fallers and non-fallers aged 85 and older. 64 participants aged 85 and older took part in this case control study. The case group (fallers, n = 32) had experienced falls to the ground in the 6 months prior to the assessment. SPARC analyses were conducted in all phases of the single and dual task iTUGs. We also performed correlation mapping to test the relation of socio-demographic and clinical features on SPARC metrics. The magnitude of between-group differences was calculated using D-Cohen effect size (ES). SPARC was able to distinguish fallers during the single iTUG (ES ≈ 4.18). Turning while walking in the iTUG induced pronounced unsmooth movements in the fallers (SPARC ≈ -13; ES = 3.52) and was associated with the ability to maintain balance in the functional reach task. This information is of importance in the study of functional mobility in the oldest-old and to assess the efficacy of fall-prevention programs.


The clinical manifestations of lithium intoxication.
Lithium has been a part of the psychiatric pharmacopoeia for more than half a century. Its efficacy is marred by a narrow therapeutic index and significant toxicity. To increase physicians' awareness of the various manifestations of lithium intoxication. We reviewed the clinical data of cases of lithium poisoning occurring in a municipal hospital during a 10 year period. Eight patient records were located. The mortality rate was 12.5%. All patients were women and the mean age was 66.4 years. The most common symptoms were neurologic. One illustrative case is described in detail with lithium serum levels showing the usual two-phase decline. Lithium poisoning can present in many forms. Increased physician awareness and the early use of effective treatment, mainly hemodialysis, will prevent mortality and protracted morbidity associated with this condition.


Effects of a synthetic prostanoid, rosaprostol, on the changes of gastric acidity and digestive disorders induced by NSAID.
In 24 subjects without upper gastrointestinal lesions, gastric pH was measured from 30 min before until 90 min after the administration of diclofenac sodium (50 mg), piroxicam (20 mg), or 500 mg acetylsalicylic acid. In all these cases a drop of gastric pH was recorded, which started with all the drugs 15 min after their administration and lasted throughout the recording. Pre-treatment with rosaprostol (2 g given 30 min before the start of the trial) prevented the drop in pH. Twenty subjects with chronic joint diseases were divided into two groups in a cross-over double-blind randomized experimental design. One group received piroxicam (20 mg) + rosaprostol (2 g) daily; the other group was treated with piroxicam 20 mg + placebo. The patients were clinically reviewed every week in a month and questioned about their symptoms. Statistical analysis demonstrated that patients with articular diseases treated with NSAIDs + rosaprostol exhibited a frequency and severity of symptoms lower than those recorded in subjects receiving NSAIDs + placebo. Rosaprostol was found to be capable of antagonizing the variations of gastric acid output induced by the oral administration of NSAIDs, and to prevent and treat the occurrence of digestive disorders when given in combination with NSAIDs. These effects result from the action of rosaprostol on the mucosal barrier, and this cytoprotective action is confirmed by the present study with continuous measurements of gastric pH.


The culture of obesity.
The purpose of this article is to provide nurses with a model for the culture of obesity to more fully understand this distinct cultural group. Although individuals from all walks of life are affected by obesity, it occurs at higher rates among specific ethnic groups such as African-Americans. Obesity puts African-Americans at further risk for health problems such as diabetes, hypertension and heart disease. In seeking culturally responsive interventions for African-Americans who are obese, it is important to realize that they belong to two cultural groups; the African-American culture and the culture of obesity. It is hoped that knowledge regarding the culture of obesity, coupled with the nurses pre-exiting knowledge about the culture of African-Americans, will provide a foundation for the development of culturally responsive nursing interventions for African-Americans who are obese. The authors utilized Giger and Davidhizar's Transcultural Assessment Model (1999), as the guiding framework to present a model of the culture of obesity.


Perspectives on Machine Learning for Classification of Schizotypy Using fMRI Data.
Functional magnetic resonance imaging is capable of estimating functional activation and connectivity in the human brain, and lately there has been increased interest in the use of these functional modalities combined with machine learning for identification of psychiatric traits. While these methods bear great potential for early diagnosis and better understanding of disease processes, there are wide ranges of processing choices and pitfalls that may severely hamper interpretation and generalization performance unless carefully considered. In this perspective article, we aim to motivate the use of machine learning schizotypy research. To this end, we describe common data processing steps while commenting on best practices and procedures. First, we introduce the important role of schizotypy to motivate the importance of reliable classification, and summarize existing machine learning literature on schizotypy. Then, we describe procedures for extraction of features based on fMRI data, including statistical parametric mapping, parcellation, complex network analysis, and decomposition methods, as well as classification with a special focus on support vector classification and deep learning. We provide more detailed descriptions and software as supplementary material. Finally, we present current challenges in machine learning for classification of schizotypy and comment on future trends and perspectives.


Once-weekly epoetin-beta improves hemoglobin levels in cancer patients with chemotherapy-induced anemia: A randomized, double-blind, dose-finding study.
To determine a recommended dose of once-weekly epoetin-beta administration for anemic cancer patients receiving myelosuppressive chemotherapy, we conducted a multicenter, randomized, double-blind trial. A total of 86 patients with malignant lymphoma or lung cancer who received chemotherapy containing platinum, taxanes or anthracyclines were enrolled in the study. Patients were randomly assigned into groups that received three dose levels of epoetin-beta (9000, 18,000 or 36,000 IU) administered subcutaneously once a week for 12 weeks. The primary endpoint was change in hemoglobin, while the secondary endpoints were quality of life (QOL) assessed by Functional Assessment of Cancer Therapy-Anemia (FACT-An) questionnaire and transfusion requirements. Among the 69 patients (per protocol set population) assessable for efficacy, hemoglobin level change in the 36,000 IU group was significantly greater than that in the 9000 IU group (1.75 +/- 2.15 versus 0.04 +/- 1.98 g/dl; P = 0.009), and a significant dose-response relationship was observed for the change in hemoglobin level (P = 0.003). Although changes in FACT-An Total Fatigue subscale (Fatigue subscale) scores were similar for the three dosage groups, there was a statistically significant correlation (r = 0.435, P < 0.001) between the change in hemoglobin levels and the change in Fatigue subscale scores. The proportion of transfused patients was significantly smaller in the 36 000 IU group compared with that in the 9000 IU group (P = 0.022, not adjusted for pre-study transfusions). The incidence of adverse events was similar in the three dosage groups. Once-weekly epoetin-beta 36,000 IU for 12 weeks was well tolerated and significantly increased hemoglobin levels in anemic cancer patients receiving chemotherapy.